This invention relates to improved methods of manufacturing or processing polymeric biomedical devices, particularly ophthalmic biomedical devices, including contact lenses, intraocular lenses and ophthalmic implants. Specifically, this invention is related to extraction of unreacted monomers or oligomers from such devices.
Ophthalmic biomedical devices, such as intraocular lenses, contact lenses or ophthalmic implants, may be made from a variety of polymeric materials. For example, silicone hydrogel contact lenses are made from a monomer mixture containing hydrophilic and hydrophobic comonomers. The lenses are made by exposing this monomer mixture to heat (thermal polymerization), to UV radiation (UV polymerization) or other electromagnetic irradiation, or combinations thereof, thereby curing the monomer mixture to form a copolymeric material. The monomer mixture may be cast in a mold having a molding cavity corresponding to the desired contact lens shape. Alternately, a rod, cylindrical button, or other shaped article may be cast, and then cut into lenses. Diluents are sometimes used to reduce the incompatibility between the hydrophilic and hydrophobic monomers in the monomer mixture and to improve curing efficiency. The diluents are not polymerized and must eventually be removed from the cured polymer.
Generally, in the manufacture of such lenses, some of the monomers in the monomer mixture do not completely polymerize, resulting in unreacted monomers remaining in the lens. Further, the polymerization process may result in partially reacted oligomers remaining in the lens matrix. Additionally, additives from the mold may migrate into the lens material. Failure to perform an extraction step to remove such undesired materials from the lens may cause eye irritation or the lens may have reduced optical clarity and reduced biocompatibility. Additionally, there is concern with the possibility of ocular damage which may occur upon wearing an unextracted lens. The extraction of any lens contaminants generally should be as complete as possible.
A well-known method of extracting a contact lens involves placing the lens in an alcohol solution (e.g., isopropyl alcohol (IPA)) for several hours followed by a water extraction. The alcohol extracts hydrophobic or hydrophilic materials, including materials that have relatively low water solubility, while the water will extract water soluble residues. The water extraction will also remove any alcohol extraction solution that may have remained in the lens material. The extracting water may be heated to facilitate the extraction. While this extraction process is fairly efficient in removing materials from the lens, extraction by this process often generates volumes of contaminated solvent which may cause disposal and environmental problems.
As mentioned, a contact lens may be cast in a mold and then removed from the mold. After solvent reduction, which sometimes involves drying the lens in an oven, the lens is in a dry state. This allows the lens to be easily edged and surface treated, if necessary. The lens must be in a dry and unwarped state to undergo edging, surface treatment or handling. After this processing, the lens is extracted and/or hydrated with water or an aqueous solution. Inspection, packaging and sterilization of the lens may then be completed.
Since a lens must be in a dry state for various surface treatment processes, the lens is conventionally surface treated prior to extraction with a solvent such as isopropyl alcohol (IPA) and extraction/hydration with water. The IPA swells the lenses significantly, and this expansion may crack or otherwise deleteriously affect the lens surface coating. Since it is important to retain the surface coating, a different and more efficient process is desirable. Water also expands the lens but to a much lesser extent than IPA.
Other methods have been used to extract cured contact lenses. One method involves extracting with a solvent such as carbon dioxide, either in a supercritical state or at standard temperature and pressure. When the solvent is in a supercritical state, it has density and solvating strength approaching that of a liquid but the properties of a gas, such as high diffusivity and low viscosity. Carbon dioxide (CO2) is often used as the solvent since it is environmentally friendly; it has a moderate critical temperature of 31xc2x0 C. and a critical pressure of about 75 bar or 1100 psi.
By exposing a cured contact lens to supercritical or liquid carbon dioxide (CO2), unreacted or incompletely polymerized material in the polymeric structure can be removed. WO 95/20476 (Bawa et al) discloses such a method. Supercritical carbon dioxide can be used to extract incompletely polymerized residual material from contact lens materials. By using a supercritical fluid such as carbon dioxide for extraction, as opposed to a liquid solvent, the lens is left in a dry and unwarped state. This has significant advantages in downstream processing. For example, a lens extracted in supercritical fluid can be edged and surface coated after extraction. WO 95/20476 (Bawa et. al.) also discloses adding a co-solvent such as IPA to the carbon dioxide. Other references also disclosing the use of carbon dioxide, with or without IPA, are WO 96/26059 (Hoffman et al) and WO 98/07554 (Terry et al).
The present invention provides a method of treating ophthalmic biomedical devices including contact lenses, intraocular lenses and ophthalmic implants. This treatment renders the device safe for prolonged contact with ocular tissue and, in the case of contact lenses, comfortable for wear.
According to certain embodiments, this invention provides a method of extracting unreacted or incompletely polymerized materials from the device by varying the concentration of a primary solvent, such as carbon dioxide, and a co-solvent, such as isopropanol. During the extraction process, the concentration of the co-solvent is pulsed. By xe2x80x9cpulsingxe2x80x9d, it is meant that the concentration of the co-solvent begins at a lower first amount and then is increased to a second higher amount. The concentration is then returned to the lower first amount. This is considered to be a single pulse or one cycle. As the amount of the co-solvent is increased, the device expands in dimension, i.e., the diameter and center thickness increase. By reducing the amount of co-solvent, the device shrinks. Multiple pulses are preferred. During each pulse, the device goes through one cycle of expansion and shrinkage. After the extraction, the device is exposed to supercritical primary solvent which serves to dry the device. Following depressurization, the devices are recovered in a dry and unwarped state, and the devices can be further processed easily. As this extraction is done prior to surface treatment, there is no concern that coatings on the devices will be detrimentally affected by a subsequent extraction step; rather, surface treatment can be performed after recovering the dry device.
According to further embodiments, a device is extracted while retained in a portion of the mold. The device is released from the mold in which it was formed by the cycle(s) of expansion and shrinkage.
Specific embodiments of the invention include a method of extracting a polymeric, ophthalmic biomedical device comprising: (a) subjecting said device to a primary solvent; (b) subjecting said device to a mixture of a co-solvent and the primary solvent for a predetermined period of time; and (c) subjecting said device to the primary solvent for a predetermined time such that said device is in a dry state, wherein said ocular medical device goes through at least one cycle of expansion and shrinkage. Another specific embodiment includes a method of extracting a polymeric, ophthalmic biomedical device contained within a chamber, said method comprising: (a) subjecting said device to a supercritical fluid for a first predetermined time in said chamber; (b) introducing isopropyl alcohol into said chamber to obtain a first mixture including a first predetermined level of isopropyl alcohol and subjecting said device to said first mixture for a second predetermined period of time; (c) reducing the amount of isopropyl alcohol within said chamber to a second, lowered predetermined level and subjecting said device to the mixture for a third predetermined period of time; and (d) subjecting said device to supercritical fluid for a fourth predetermined time such that said lens is in a dry state, wherein said device goes through at least one cycle of expansion and shrinkage.
Another embodiment provides a method of extracting a contact lens retained in the mold in which it was cast, comprising: subjecting the lens to alternating concentrations of a supercritical fluid and a co-solvent, such that said contact lens goes through at least one cycle of expansion and shrinkage and whereby the contact lens is released from the mold. The invent also provides a process of making a contact lens comprising: (a) casting said lens in a two-part mold assembly; (b) removing a first mold portion such that said lens is retained in a second mold portion; (c) extracting said lens with mixture of a supercritical fluid and a solvent and releasing said lens from said second mold portion; (d) subjecting the lens to supercritical fluid, whereby a dry lens is obtained; (e) surface treating said dry lens such that at least one lens said surface is rendered hydrophilic; and (f) hydrating and packaging said lens.
The invention also provides a method of extracting an ocular medical device comprising, sequentially: (a) subjecting said device to a supercritical primary solvent, or a first mixture of a supercritical primary solvent and a co-solvent, in a chamber; (b) subjecting said device to a second mixture of the supercritical primary solvent and a co-solvent in the chamber, wherein the concentration of the extracting co-solvent is higher than the first mixture; (c) reducing the level of the extracting co-solvent in the chamber; (d) repeating steps (a) through (c); and (e) subjecting said device to the supercritical primary solvent to dry the device.